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Histology of anal cancer

The anal canal has short zones covered with different types of epithelium from proximal to distal end.

  • Rectal zone with colonic type of mucosa
  • Transitional zone varying with colonic mucosa and squamous epithelium
  • Squamous epithelium zone with non-keratinizing squamous epithelium
  • Perianal skin with keratinizing squamous cell epithelium

Carcinoma in the anal canal generally originate from the squamous epithelium in the distal part of the canal, but can also originate from cylindrical epithelium in the colonic mucosa or perianal glands in the transitional zone. Most adenocarcinoma in the proximal zone will be designated as distal carcinomas primary in the rectum.

Carcinoma precursor lesions

  • Anal Intraepithelial Neoplasia (AIN) (Bowen`s Disease)
  • Paget's disease
  • Adenomas (tubular, tubulo-villous, villous) in distal rectum/proximal anal canal

Carcinoma percursor lesions in the anal canal (AIN) are classified in the same way as cervical intraepithelial lesions (CIN).

AIN is divided into:

  • mild (grade 1)
  • moderate (grade 2)
  • severe dysplasia/carcinoma in situ (grade 3)

or into:

  • low-grade
  • high-grade intraepithelial neoplasia

High-grade intraepithelial neoplasia includes moderate and severe dysplasia. These lesions can appear as condylomas or flat lesions. The majority of in situ lesions and infiltrating squamous cell carcinomas are associated with HPV.

An uncommon (infrequent) intraepithelial lesion is the ”extramammary Paget's disease”. This lesion appears as skin eczema and histologically atypical mucosa, containing cells seen in the squamous epithelium. In about half of these cases, the patient also demonstrates a simultaneous rectal or colonic adenocarcinoma. In the other half, this lesion is believed to originate from apocrine glands. These have a strong recurrence tendency and can infiltrate.

Adenomas in the proximal anal canal will, in most cases, be considered rectal adenomas.

Classification and differentiation

The vast majority of anal canal carcinomas are squamous cell carcinomas. They can be keratinizing or non-keratinizing. Basaloid squamous cell carcinomas demonstrate significant basal cell appearance. This type should not be misdiagnosed as basal cell carcinomas in perianal skin, since they have much better prognoses. Squamous cell carcinomas in perianal skin have better prognoses than squamous cell carcinoma in the anal canal. In extensively growing squamous cell carcinomas it may be difficult to determine the correct origin and thus prognosis.

Photomicrograph demonstrating carcinoma in situ in the anal canal. Click to magnify. Photomicrograph demonstrating (Mb Bowen) carcinoma in situ in the skin of the anal canal. Click to magnify. Photomicrograph demonstrating squamous cell carcinoma in the anal canal. Click to magnify.

Verrucous carcinomas also designated as ”giant condyloma” (Buschke-Löwenstein tumor), are macroscopically cauliflower in shape. This tumor can grow in the perineum, perianally, and up in the anus, isolated in the rectum or on the penis. This tumor can also infiltrate vagina, rectum, and the urinary tract. This tumor is diagnosed when the size is up to 30 cm in diameter.

Histologically, the verrucous carcinomas show acanthosis and papillomatosis, and lack cellular atypia and definite stromal infiltration.

Adenocarcinomas in the anal canal can represent downgrowth from rectal carcinomas or originate from the rectal zone of the anal canal. Adenocarcinomas originating from the transitional zone appear like the above mentioned adenocarcinomas and do not seem to represent a special histological type. Although, adenocarcinomas can appear in the extramucosal part of the anal canal and originate from anorectal fistulas (Crohn's disease) or from anal glands. Both of these types of adenocarcinomas can appear as mucinous cysts and be highly differentiated adenocarcinomas. Anal adenocarcinomas can be very aggressive tumors.

Other tumor types:

  • Small cell carcinoma
  • Undifferentiated carcinoma
  • Endocrine tumors and carcinomas (carcinoid)
  • Malignant melanoma
  • GIST and other mesenchymal tumors
  • Malignant lymphomas

Fixation of the operation specimens

The specimen is cut open and cleaned before fixation in formalin. It is advantagous if the specimen is fixed by needle to a cork plate. This facilitates the evaluation of resection borders.

Pathology report

The pathology report on an operation specimen should include the following:

  • Localization (over/under ”pectinated line,” perianal skin)
  • Size
  • Classification
  • Grading
  • Infiltration depth
  • Number of lymph nodes with and without metastases
  • Tumor relation to resection borders
  • Blood vessel invasion
  • Perineural invasion
  • pTNM

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